Increased levels of regulatory T cells (T(regs)) in human immunodeficiency virus-infected patients after 5 years of highly active anti-retroviral therapy may be due to increased thymic production of naive T(regs)

L Kolte; J C Gaardbo; K Skogstrand; L P Ryder; A K Ersbøll; Susanne Dam Poulsen (tidl. Nielsen)

doi:10.1111/j.1365-2249.2008.03803.x

Increased levels of regulatory T cells (T(regs)) in human immunodeficiency virus-infected patients after 5 years of highly active anti-retroviral therapy may be due to increased thymic production of naive T(regs)

L Kolte, J C Gaardbo, K Skogstrand, L P Ryder, A K Ersbøll, Susanne Dam Poulsen (tidl. Nielsen)

Department of Clinical Medicine

37 Citations (Scopus)

Abstract

Summary This study determines levels of regulatory T cells (T(regs)), naive T(regs), immune activation and cytokine patterns in 15 adult human immunodeficiency virus (HIV)-infected patients receiving prolonged highly active anti-retroviral therapy (HAART) who have known thymic output, and explores if naive T(regs) may represent recent thymic emigrant T(regs). HIV-infected patients treated with HAART with a median of 1 and 5 years were compared with healthy controls. Percentages of T(regs) (CD3(+)CD4(+)CD25(+)CD127(low)), naive T(regs) (CD3(+)CD4(+)CD25(+)CD45RA(+)) and activation markers (CD38(+)human leucocyte antigen D-related) were determined by flow cytometry. Forkhead box P3 mRNA expression and T cell receptor excision circles (T(REC)) content in CD4(+) cells were determined by polymerase chain reaction and cytokines analysed with Luminex technology. Levels of T(regs) were significantly higher in HIV-infected patients compared with controls, both after 1 and 5 years of HAART (P < 0.001), despite fully suppressed HIV-RNA and normalization of both CD4 counts, immune activation and cytokine patterns. Furthermore, levels of naive T(regs) were elevated significantly in HIV-infected patients (P < 0.001) and were associated with thymic output measured as the T(REC) frequency in CD4(+) cells (P = 0.038). In summary, T(reg) levels in HIV-infected patients are elevated even after 5 years of HAART. Increased thymic production of naive T(regs) may contribute to higher T(reg) levels in HIV-infection.

Original language	English
Journal	Clinical and Experimental Immunology
Volume	155
Issue number	1
Pages (from-to)	44-52
ISSN	0009-9104
DOIs	https://doi.org/10.1111/j.1365-2249.2008.03803.x
Publication status	Published - 2008

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Kolte, L., Gaardbo, J. C., Skogstrand, K., Ryder, L. P., Ersbøll, A. K., & Poulsen (tidl. Nielsen), S. D. (2008). Increased levels of regulatory T cells (T(regs)) in human immunodeficiency virus-infected patients after 5 years of highly active anti-retroviral therapy may be due to increased thymic production of naive T(regs). Clinical and Experimental Immunology, 155(1), 44-52. https://doi.org/10.1111/j.1365-2249.2008.03803.x

Increased levels of regulatory T cells (T(regs)) in human immunodeficiency virus-infected patients after 5 years of highly active anti-retroviral therapy may be due to increased thymic production of naive T(regs). / Kolte, L; Gaardbo, J C; Skogstrand, K et al.
In: Clinical and Experimental Immunology, Vol. 155, No. 1, 2008, p. 44-52.

Research output: Contribution to journal › Journal article › Research › peer-review

Kolte, L, Gaardbo, JC, Skogstrand, K, Ryder, LP, Ersbøll, AK & Poulsen (tidl. Nielsen), SD 2008, 'Increased levels of regulatory T cells (T(regs)) in human immunodeficiency virus-infected patients after 5 years of highly active anti-retroviral therapy may be due to increased thymic production of naive T(regs)', Clinical and Experimental Immunology, vol. 155, no. 1, pp. 44-52. https://doi.org/10.1111/j.1365-2249.2008.03803.x

Kolte L, Gaardbo JC, Skogstrand K, Ryder LP, Ersbøll AK, Poulsen (tidl. Nielsen) SD. Increased levels of regulatory T cells (T(regs)) in human immunodeficiency virus-infected patients after 5 years of highly active anti-retroviral therapy may be due to increased thymic production of naive T(regs). Clinical and Experimental Immunology. 2008;155(1):44-52. doi: 10.1111/j.1365-2249.2008.03803.x

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abstract = "Summary This study determines levels of regulatory T cells (T(regs)), naive T(regs), immune activation and cytokine patterns in 15 adult human immunodeficiency virus (HIV)-infected patients receiving prolonged highly active anti-retroviral therapy (HAART) who have known thymic output, and explores if naive T(regs) may represent recent thymic emigrant T(regs). HIV-infected patients treated with HAART with a median of 1 and 5 years were compared with healthy controls. Percentages of T(regs) (CD3(+)CD4(+)CD25(+)CD127(low)), naive T(regs) (CD3(+)CD4(+)CD25(+)CD45RA(+)) and activation markers (CD38(+)human leucocyte antigen D-related) were determined by flow cytometry. Forkhead box P3 mRNA expression and T cell receptor excision circles (T(REC)) content in CD4(+) cells were determined by polymerase chain reaction and cytokines analysed with Luminex technology. Levels of T(regs) were significantly higher in HIV-infected patients compared with controls, both after 1 and 5 years of HAART (P < 0.001), despite fully suppressed HIV-RNA and normalization of both CD4 counts, immune activation and cytokine patterns. Furthermore, levels of naive T(regs) were elevated significantly in HIV-infected patients (P < 0.001) and were associated with thymic output measured as the T(REC) frequency in CD4(+) cells (P = 0.038). In summary, T(reg) levels in HIV-infected patients are elevated even after 5 years of HAART. Increased thymic production of naive T(regs) may contribute to higher T(reg) levels in HIV-infection.",

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AU - Kolte, L

AU - Gaardbo, J C

AU - Skogstrand, K

AU - Ryder, L P

AU - Ersbøll, A K

AU - Poulsen (tidl. Nielsen), Susanne Dam

PY - 2008

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N2 - Summary This study determines levels of regulatory T cells (T(regs)), naive T(regs), immune activation and cytokine patterns in 15 adult human immunodeficiency virus (HIV)-infected patients receiving prolonged highly active anti-retroviral therapy (HAART) who have known thymic output, and explores if naive T(regs) may represent recent thymic emigrant T(regs). HIV-infected patients treated with HAART with a median of 1 and 5 years were compared with healthy controls. Percentages of T(regs) (CD3(+)CD4(+)CD25(+)CD127(low)), naive T(regs) (CD3(+)CD4(+)CD25(+)CD45RA(+)) and activation markers (CD38(+)human leucocyte antigen D-related) were determined by flow cytometry. Forkhead box P3 mRNA expression and T cell receptor excision circles (T(REC)) content in CD4(+) cells were determined by polymerase chain reaction and cytokines analysed with Luminex technology. Levels of T(regs) were significantly higher in HIV-infected patients compared with controls, both after 1 and 5 years of HAART (P < 0.001), despite fully suppressed HIV-RNA and normalization of both CD4 counts, immune activation and cytokine patterns. Furthermore, levels of naive T(regs) were elevated significantly in HIV-infected patients (P < 0.001) and were associated with thymic output measured as the T(REC) frequency in CD4(+) cells (P = 0.038). In summary, T(reg) levels in HIV-infected patients are elevated even after 5 years of HAART. Increased thymic production of naive T(regs) may contribute to higher T(reg) levels in HIV-infection.

AB - Summary This study determines levels of regulatory T cells (T(regs)), naive T(regs), immune activation and cytokine patterns in 15 adult human immunodeficiency virus (HIV)-infected patients receiving prolonged highly active anti-retroviral therapy (HAART) who have known thymic output, and explores if naive T(regs) may represent recent thymic emigrant T(regs). HIV-infected patients treated with HAART with a median of 1 and 5 years were compared with healthy controls. Percentages of T(regs) (CD3(+)CD4(+)CD25(+)CD127(low)), naive T(regs) (CD3(+)CD4(+)CD25(+)CD45RA(+)) and activation markers (CD38(+)human leucocyte antigen D-related) were determined by flow cytometry. Forkhead box P3 mRNA expression and T cell receptor excision circles (T(REC)) content in CD4(+) cells were determined by polymerase chain reaction and cytokines analysed with Luminex technology. Levels of T(regs) were significantly higher in HIV-infected patients compared with controls, both after 1 and 5 years of HAART (P < 0.001), despite fully suppressed HIV-RNA and normalization of both CD4 counts, immune activation and cytokine patterns. Furthermore, levels of naive T(regs) were elevated significantly in HIV-infected patients (P < 0.001) and were associated with thymic output measured as the T(REC) frequency in CD4(+) cells (P = 0.038). In summary, T(reg) levels in HIV-infected patients are elevated even after 5 years of HAART. Increased thymic production of naive T(regs) may contribute to higher T(reg) levels in HIV-infection.

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